The present invention generally relates to optical imaging systems, optical probes thereof, and methods thereof for providing images of spatial or temporal distribution of chromophores or properties thereof in a physiological medium. In particular, the present invention relates to a self-calibrating optical imaging system. The present invention is applicable to optical imaging systems whose operation is based on wave equations such as the Beer-Lambert equation, modified Beer-Lambert equation, photon diffusion equation, and their equivalents.
Near-infrared spectroscopy has been used to measure various physiological properties in animal and human subjects. The basic principle underlying the near-infrared spectroscopy is that a physiological medium such as tissues and cells includes a variety of light-absorbing and light-scattering chromophores which can interact with electromagnetic waves transmitted thereto and traveling therethrough. For example, human tissues include numerous chromophores among which deoxygenated and oxygenated hemoglobins are the most dominant chromophores in the spectrum range of 600 nm to 900 nm. Therefore, the near-infrared spectroscope has been applied to measure oxygen levels in the physiological medium in terms of tissue hemoglobin oxygen saturation (or simply xe2x80x9coxygen saturationxe2x80x9dhereinafter). Technical background for the near-infrared spectroscopy and diffuse optical imaging has been discussed in, e.g., Neuman, M. R., xe2x80x9cPulse Oximetry: Physical Principles, Technical Realization and Present Limitations,xe2x80x9d Adv. Exp. Med. Biol., vol. 220, p.135-144, 1987, and Severinghaus, J. W., xe2x80x9cHistory and Recent Developments in Pulse Oximetry,xe2x80x9d Scan. J Clin. and Lab. Investigations, vol. 53, p.105-111, 1993.
Various techniques have been developed for the near-infrared spectroscopy, including time-resolved spectroscopy (TRS), phase modulation spectroscopy (PMS), and continuous wave spectroscopy (CWS). In a homogeneous, semi-infinite model, the TRS and PMS are generally used to solve the photon diffusion equation, to obtain the spectra of absorption coefficients and reduced scattering coefficients of the physiological medium, and to estimate concentrations of the oxygenated and deoxygenated hemoglobins and oxygen saturation. The CWS has generally been used to solve the modified Beer-Lambert equation and to calculate changes in the concentrations of the oxygenated as well as deoxygenated hemoglobin.
Despite their capability of providing hemoglobin concentrations as well as the oxygen saturation, the major disadvantage of the TRS and PMS is that the equipment has to be bulky and, therefore, expensive. The CWS may be manufactured at a lower cost but is generally limited in its utility, for it can estimate only the changes in the hemoglobin concentrations but not the absolute values thereof. Accordingly, the CWS cannot provide the oxygen saturation. The prior art technology also requires a priori calibration of optical probes before their clinical application by, e.g., measuring a baseline in a reference medium or in a homogeneous portion of the medium. Furthermore, all prior art technology employs complicated image reconstruction algorithms to generate images of two-dimensional and/or three-dimensional distribution of the chromophore properties.
Therefore, there exist needs for an efficient, compact, and relatively cheap optical imaging system which self-calibrates itself without relying on external measurement or data and which provides two- and/or three-dimensional images on a substantially real time basis.
The present invention generally relates to optical imaging systems, optical probes, signal and/or image processing algorithms, and methods thereof for providing two-or three-dimensional images of spatial or temporal distribution of chromophores or their properties in a physiological medium. More particularly, the present invention relates to novel self-calibrating optical imaging systems and methods thereof.
In one aspect of the present invention, an optical imaging system is provided to generate images of distribution of chromophores or their properties in target areas of various physiological media. The optical imaging system includes at least one wave source arranged to irradiate electromagnetic waves into the target areas of the medium and at least one wave detector arranged to detect electromagnetic waves from the target areas and to generate output signal in response thereto. The optical imaging system further includes an optical probe, a signal analyzer, and a signal processor. The optical probe typically includes the wave source and wave detector. The signal analyzer receives, from the wave detector, a first output signal which is representative of the distribution of the chromophores or their properties in a first target area of the medium. The signal analyzer analyzes an amplitude of each point of the first output signal and selects one or more points or portions of the first output signal having substantially similar first amplitudes. The signal processor calculates a first baseline from the first output signal, where the first baseline generally corresponds to a representative amplitude of the first amplitudes of the foregoing points or portions, and provides a self-calibrated first output signal by manipulating the first output signal and first baseline thereof. Therefore, the optical imaging system provides the self-calibrated output signal representing a spatial distribution and/or temporal variation of the chromophores or their properties in the first target area.
The foregoing optical imaging systems, probes, algorithms, and methods (collectively referred to as xe2x80x9coptical imaging systemxe2x80x9d or xe2x80x9coptical probexe2x80x9d hereinafter) of the present invention provide numerous advantages. Contrary to the prior art optical imaging devices that require a priori measurement and estimation of an output signal baseline in a reference medium (or area) before their clinical applications, the optical imaging system of the present invention allows a user to directly scan a target area, to obtain the output signal, and to simultaneously obtain the baseline of the output signal. Accordingly, the optical imaging system of the present invention obviates the need for a prior estimation of the baseline in other reference media (or areas). In addition, because the foregoing optical imaging system can estimate the baseline and the output signals from the same target area, it does not suffer from noises or errors attributed to different optical characteristics between the reference and target areas. Furthermore, due to simpler algorithms for estimating the baseline, the optical imaging system of the present invention allows real-time calibration of the output signals and, therefore, contributes to the real-time construction of images of the distribution of the chromophore or its properties.
Embodiments of this aspect of the present invention includes one or more of the following features.
The optical probe includes a scanning area which is almost equal to or as large as at least a substantial portion of the first target area of the medium. Multiple wave sources and detectors are disposed in the scanning area so that the chromophore properties in the first target area can be measured by a single measurement in the first target area. In the alternative, the optical probe may include a scanning area which may be only a small region of the first target area. In this embodiment, the optical imaging system includes an actuator member arranged to move at least one of the wave source and wave detector so that at least a substantial portion of the first target area can be scanned thereby. Accordingly, the wave detector can generate multiple first output signals while the optical probe or its main housing is positioned and maintained stationary in the first target area. This embodiment allows construction of compact optical probes with a minimal number of the wave sources and/or detectors implemented thereto. In addition, such optical probes can minimize the noises or errors attributed to idiosyncratic component variations among system components.
The foregoing optical imaging system may also include an image processor which constructs the images of the distribution of the chromophores or properties thereof from the self-calibrated first output signals, preferably on a substantially real-time basis. The signal analyzer and processor may also operate on a substantially real-time basis and provide the self-calibrated first output signal without displacing the optical probe from the first target area. The optical imaging system may further include a memory for storing the first output signal, first baseline, self-calibrated first output signal, and other signals or data.
The signal analyzer may include a threshold unit for obtaining a threshold amplitude, a comparison unit for comparing the amplitudes of the points or portions of the first output signal with the threshold amplitude, and a selection unit for identifying multiple selected points or portions of the first output signal. The threshold unit may receive the threshold amplitude from a user. Alternatively, the threshold unit may calculate a reference amplitude based on the first output signal and then calculate the threshold amplitude from the reference amplitude, where the reference amplitude may be, e.g., a local maximum or minimum of the first output signal measured in the first target area, an average of at least one or entire portion of the first output signal, a global maximum or minimum of multiple output signals measured in multiple target areas over the medium, and their combinations. The threshold amplitude may be calculated as a product of the reference amplitude and a pre-determined factor which may be encoded therein or may be provided by the operator. Therefore, depending on the mode of selecting the threshold amplitude, the first amplitudes of the selected points or portions may be either greater or less than the threshold amplitude.
Alternatively, the signal analyzer may include a threshold unit for obtaining a threshold range of amplitudes, a comparison unit for comparing the amplitudes of the points or portions of the first output signal with the threshold range, and a selection unit arranged to identify those selected points or portions of the first output signal. Accordingly, the first amplitudes of the selected points may fall within or outside the threshold range.
The signal analyzer may also include a filter unit arranged to improve signal-to-noise ratio of the first output signals. The filter unit may include an algorithm arranged to arithmetically, geometrically, weight- or ensemble-averaging multiple first output signals. The filter unit may also include a low pass filter for removing high frequency noises from the first output signal.
The signal processor may include an averaging unit for calculating the first baseline by arithmetically, geometrically, weight- or ensemble-averaging the substantially similar first amplitudes of the foregoing points or portions. The signal processor may also include a calibration unit for obtaining the self-calibrated first output signal by normalizing the first output signal by its first baseline, where the self-calibrated first output signal may be defined as a ratio of the first output signal to the first baseline or a ratio of a difference between the first output signal and first baseline to the first baseline.
The signal analyzer may also include a control unit which stores multiple baselines measured in multiple target areas and compares one or each baseline from the others thereof. The control unit may calculate an average of such multiple baselines. The control unit may be arranged send a signal or alarm to the operator when at least one of the baselines is at least substantially different from at least one of the others.
In another aspect of the invention, an optical imaging system is provided to generate images of distribution of chromophores or their properties in target areas of a physiological medium. The optical imaging system includes at least one of the foregoing wave sources and at least one of the foregoing wave detectors. The optical imaging system also includes a signal analyzer, signal processor, and image processor. The signal analyzer receives, from the wave detector, a first output signal representative of the foregoing distribution in a first target area of the medium, analyzes amplitudes of the first output signal, and selects multiple points or portions of the first output signal having substantially similar first amplitudes. The signal processor calculates, from the first output signal, a first baseline which corresponds to a representative value of the first amplitudes, and provides a self-calibrated first output signal by manipulating both of the first output signal and its first baseline. The image processor constructs the images of the foregoing distribution from the self-calibrated first output signals.
In yet another aspect of the present invention, an optical imaging system is provided to generate images of the foregoing distribution in target areas of a physiological medium. The optical imaging system includes at least one of the foregoing wave sources and at least one of the foregoing wave detectors along with a movable member, actuator member, signal analyzer, signal processor, and image processor. The movable member includes at least one of the wave source and detector, and the actuator member generates at least one movement of the movable member. The signal analyzer receives, from the wave detector, a first output signal representing the foregoing distribution in a first target area of the medium, analyzes an amplitude of each point of the first output signal, and selects multiple points or portions of the first output signal having substantially similar first amplitudes. The signal processor calculates, from the first output signal, a first baseline which corresponds to a representative amplitude of the first amplitudes, and provides a self-calibrated first output signal by manipulating the first output signal and its first baseline. The image processor then constructs the images of the foregoing distribution from the self-calibrated first output signals.
In a further aspect of the present invention, a method is provided to obtain a calibrated output signal from an optical imaging system which includes an optical probe with the foregoing wave source and detector. The method includes the steps of positioning the optical probe on a first target area of said medium, generating a first output signal without displacing the optical probe from the first target area, identifying at least one first portion of the first output signal having substantially similar first amplitudes, and obtaining a first baseline of the first output signal from a representative value of the foregoing first portion having the first amplitudes.
Embodiments of this aspect of the present invention includes one or more of the following features.
The method may also include the step of normalizing the first output signal by the first baseline to provide a self-calibrated first output signal. In addition, the method may include the step of reducing noise from the first output signal prior to performing the foregoing identifying and obtaining steps. The reducing step may include the step of, e.g., arithmetically, geometrically, weight- or ensemble-averaging multiple first output signals or the step of processing at least a portion of the first output signal through a low-pass filter.
The generating step may include the step of providing movement of at least one of the wave source and detector over the different regions of the first target area, while generating the first output signal during such movement.
The identifying step may include the step of selecting a threshold amplitude and identifying the first portion of the first output signal having the amplitudes greater or less than the threshold amplitude. The identifying step may alternatively include the steps of selecting at least one threshold range and identifying the first portion which has the amplitudes within or outside the threshold range. Such selecting steps may be manually selecting the threshold amplitude and/or range, or identifying a reference amplitude or range and providing the threshold amplitude and/or range therefrom. The reference amplitude may be selected as a local maximum or minimum of the first output signal measured in the first target area, an average of one or entire portion of the first output signal, a global maximum or minimum of multiple output signals measured in multiple target areas over the medium, and a combination thereof.
The obtaining step may include one of arithmetically, geometrically, and/or weight-averaging the first amplitudes of the first portion of the first output signal.
The method may further include the steps of moving the optical probe to a second target area of the medium, generating a second output signal from the second target area, and normalizing the second output signal by the first baseline from the first-target area to provide a self-calibrated second output signal. Such moving and generating steps may also be repeated in other target areas of the medium. Alternatively, the method may include the steps of moving the optical probe to a second target area of the medium, generating a second output signal from the second target area, identifying, from the second output signal, at least one second portion having substantially similar second amplitudes, and obtaining a second baseline of the second output signal corresponding to a representative amplitude of the second amplitudes. A composite baseline may be obtained by averaging the first and second baselines by arithmetically, geometrically, weight-, and/or ensemble-averaging such baselines or by manually selecting one of the baselines as the composite baseline.
In yet another aspect of the invention, yet another method is provided to obtain a calibrated output signal from an optical imaging system including the foregoing optical probe with the foregoing wave source and detector. The method includes the steps of positioning the optical probe on a first target area of a physiological medium with a normal region and an abnormal region, generating a first output signal without displacing the optical probe from the first target area, identifying from the first output signal at least one first portion of the first output signal attributed to the normal region of the target area, and obtaining a first baseline of the first output signal from a representative value of the first portion of the first output signal.
Embodiments of this aspect of the present invention includes one or more of the following features.
The method may also include the step of normalizing the first output signal by the first baseline to provide a self-calibrated first output signal. The first portion of the first output signal may have a substantially flat profile and/or such first portion may have substantially similar first amplitudes.
In a further aspect of the present invention, yet another method is provided for calibrating an optical imaging system which includes the foregoing optical probe with the foregoing wave source and detector. Such method includes the steps of positioning the optical probe on a first target area of a physiological medium, generating a first output signal without displacing the optical probe from the first target area, identifying from the first output signal at least one first portion which has substantially similar first amplitudes before displacing the optical probe from the first target area, and obtaining a first baseline of the first output signal which is a representative value of the similar first amplitudes before displacing the optical probe from the first target area.
Embodiments of this aspect of the present invention includes one or more of the following features.
The method may include the step of normalizing the first output signal by the first baseline to provide a self-calibrated first output signal on a substantially real time basis. The method may also include the step of generating images of the first output signal, images of the self-calibrated first output signal, images derived from the first output signal, and images derived from the self-calibrated first output signal.
Each of the foregoing optical imaging systems and methods of the present invention may incorporate analytical and/or numerical solution schemes disclosed in the commonly assigned co-pending U.S. non-provisional patent application bearing Ser. No. 09/664,972, entitled xe2x80x9cA system and Method for Absolute Oxygen Saturationxe2x80x9d by Xuefeng Cheng, Xiaorong Xu, Shuoming Zhou, and Ming Wang on Sep. 18, 2000 which is incorporated herein by reference in its entirety (referred to as xe2x80x9cthe ""972 applicationxe2x80x9d hereinafter). Therefore, the absolute values of concentration of oxygenated hemoglobin, [HbO], concentration of deoxygenated hemoglobin, [Hb], oxygen saturation, [SO2], and temporal changes in blood volume may be obtained by any of the solution schemes of the co-pending ""972 application, and images thereof may be provided to allow physicians to make direct diagnosis of the target area of the medium based on the xe2x80x9cabsolutexe2x80x9d and/or xe2x80x9crelativexe2x80x9d values of the chromophore properties in the physiological media. In addition, operational characteristics of the optical imaging systems of the present invention are generally not affected by the precise number of the wave sources and/or detectors and by geometric arrangement therebetween.
As used herein, a xe2x80x9cchromophorexe2x80x9d means any substance in a physiological medium which can interact with electromagnetic waves transmitting therethrough. Such chromophore may include solvents of a medium, solutes dissolved in the medium, and/or other substances included in the medium. Specific examples of such chromophores may include, but not limited to, cytochromes, enzymes, hormones, proteins, cholesterols, lipids, apoproteins, chemotransmitters, neurotransmitters, carbohydrates, cytosomes, blood cells, cytosols, water, oxygenated hemoglobin, deoxygenated hemoglobin, and other materials present in the animal or human cells, tissues or body fluid. The xe2x80x9cchromophorexe2x80x9d may also include any extra-cellular substance which may be injected into the medium for therapeutic or imaging purposes and which may interact with electromagnetic waves. Typical examples of such chromophores may include, but not limited to, dyes, contrast agents, and/or other image-enhancing agents, each of which exhibits optical interaction with electromagnetic waves having wavelengths in a specific range.
xe2x80x9cHemoglobinsxe2x80x9d are oxygenated hemoglobin (i.e., HbO) and/or deoxygenated hemoglobin (i.e., Hb). Unless otherwise specified, xe2x80x9chemoglobinsxe2x80x9d refer to both oxygenated and deoxygenated hemoglobins. xe2x80x9cTotal hemoglobinxe2x80x9d means the sum of the oxygenated and deoxygenated hemoglobins.
xe2x80x9cElectromagnetic wavesxe2x80x9d as used herein may include acoustic or sound waves, near-infrared rays, infrared rays, visible light rays, ultraviolet rays, lasers, and/or photons.
xe2x80x9cPropertyxe2x80x9d of the chromophore refers to intensive property thereof such as concentration of the chromophore, a sum of concentrations thereof, a ratio thereof, and the like. xe2x80x9cPropertyxe2x80x9d may also refer to extensive property such as, e.g., volume, mass, weight, volumetric flow rate, and mass flow rate of the chromophore.
The term xe2x80x9cvaluexe2x80x9d is an absolute or relative value which represents spatial or temporal changes in the property of the chromophores (or hemoglobins).
xe2x80x9cDistributionxe2x80x9d refers to two-dimensional or three-dimensional distribution of the chromophores or their properties. The xe2x80x9cdistributionxe2x80x9d may be measured or estimated in a spatial and/or temporal domain.
Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood and/or used by one of ordinary skill in the art to which this invention belongs. Although methods and materials similar or equivalent to those described herein can be applied and/or used in the practice of or testing the present invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present application, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting.
Other features and advantages of the invention will be apparent from the following detailed description and from the appended claims.